Natural Product: NPC480990

Natural Product IDNPC480990
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 BGEGUEBVMMQCCD-SFHVURJKSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003642] 8-prenylated flavans
            • [CHEMONTID:0003508] 8-prenylated flavanones

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey BGEGUEBVMMQCCD-SFHVURJKSA-N
Standard InCHI InChI=1S/C21H22O7/c1-10(2)4-5-12-13(22)8-14(23)19-15(24)9-18(28-20(12)19)11-6-16(25)21(27-3)17(26)7-11/h4,6-8,18,22-23,25-26H,5,9H2,1-3H3/t18-/m0/s1
SMILES CC(=CCc1c(cc(c2C(=O)C[C@@H](c3cc(c(c(c3)O)OC)O)Oc12)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   386.14 Volume:   386.543
?
Van der Waals volume.
Dense:   0.999 LogP:   3.485
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.166
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.516
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   116.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.592 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.504 Fsp3:   0.286
MCE-18:   66.111
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.775 Fluc inhibitor:   0.641
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.557
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.609
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.333 Promiscuous compounds:   0.139

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.072 MDCK Permeability:   -4.785
Pgp-inhibitor:   0.392 Pgp-substrate:   0.021
PAMPA:   0.146
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.005
20% Bioavailability (F20%):   0.912 30% Bioavailability (F30%):   0.997
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.97
Plasma Protein Binding (PPB):   95.405% Volume Distribution (VD):   0.014
Fu: 4.026%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.994
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.968
BSEP inhibitor:   0.078

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.302 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.019 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.973
CYP3A4-inhibitor:   0.996 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  3.76 Half-life (T1/2):  1.613

ADMET: Toxicity

hERG Blockers:  0.04 hERG Blockers (10um):  0.46
Human Hepatotoxicity (H-HT):  0.756 Drug-induced Liver Injury (DILI):  0.895
AMES Toxicity:  0.786 Rat Oral Acute Toxicity:  0.911
Maximum Recommended Daily Dose:  0.758 Skin Sensitization:  0.983
Carcinogencity:  0.43 Eye Corrosion:  0.001
Eye Irritation:  0.92 Respiratory Toxicity:  0.988
Drug-induced Neurotoxicity:  0.565 Ototoxicity:  0.519
Hematotoxicity:  0.258 Drug-induced Nephrotoxicity:  0.877
Genotoxicity:  0.992 RPMI-8226 Immunitoxicity:  0.23
A549 Cytotoxicity:  0.922 Hek293 Cytotoxicity:  0.674
BCF:   1.669
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   4.094
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.746
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.907
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96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO8257 Carpha glomerata Species Cyperaceae Eukaryota n.a. n.a. n.a. PMID[30219526]
NPO8257 Carpha glomerata Species Cyperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8257 Carpha glomerata Species Cyperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



  NP Quantity Composition/Concentration

Organism ID Organism Name Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



 Biological Activity

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 5200.0 nM PMID[30219526]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC480990 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
0.8276 Intermediate Similarity NPC291878
0.807 Intermediate Similarity NPC148757
0.7414 Intermediate Similarity NPC76372
0.7414 Intermediate Similarity NPC37496
0.7288 Intermediate Similarity NPC107572
0.7288 Intermediate Similarity NPC32739
0.7258 Intermediate Similarity NPC161506
0.7097 Intermediate Similarity NPC485610
0.7049 Intermediate Similarity NPC66515
0.6769 Remote Similarity NPC24136
0.6721 Remote Similarity NPC324436
0.6721 Remote Similarity NPC78
0.6721 Remote Similarity NPC306829
0.6719 Remote Similarity NPC36217
0.6308 Remote Similarity NPC182852
0.6212 Remote Similarity NPC10990
0.6176 Remote Similarity NPC166934
0.6094 Remote Similarity NPC187282
0.6094 Remote Similarity NPC250214
0.5946 Remote Similarity NPC484417
0.5942 Remote Similarity NPC300988
0.5926 Remote Similarity NPC28918
0.5846 Remote Similarity NPC149026
0.5758 Remote Similarity NPC220998
0.5522 Remote Similarity NPC17170
0.5522 Remote Similarity NPC610133
0.5484 Remote Similarity NPC480995
0.5484 Remote Similarity NPC480992
0.5484 Remote Similarity NPC477503
0.5479 Remote Similarity NPC164272
0.5479 Remote Similarity NPC470327
0.5441 Remote Similarity NPC76338
0.5441 Remote Similarity NPC250242
0.5395 Remote Similarity NPC218226
0.5373 Remote Similarity NPC265040
0.5373 Remote Similarity NPC156190
0.5362 Remote Similarity NPC608140
0.5333 Remote Similarity NPC192686
0.5303 Remote Similarity NPC164980
0.5303 Remote Similarity NPC480991
0.5294 Remote Similarity NPC310130
0.5224 Remote Similarity NPC236766
0.5224 Remote Similarity NPC150408
0.5217 Remote Similarity NPC285555
0.5147 Remote Similarity NPC69674
0.5079 Remote Similarity NPC480993
0.5075 Remote Similarity NPC258630
0.507 Remote Similarity NPC485620
0.5065 Remote Similarity NPC488554

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC480990 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
NPD

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data